Apocrine sweat glands, comprised of ducts that open directly into the hair follicle, are largely confined to regions of the axilla and perineum (genital-anal area) and become functional just before puberty. Although this suggests that gonadal steroids (i.e. androgens and estrogens) play a role in their development, the exact hormones have not been identified.
In man, the role of the apocrine gland is unclear, since the eccrine sweat glands (which open directly onto the surface of the skin and which are distributed over nearly the entire body surface) perform the thermoregulatory function. The odor, which results from bacterial action on aprocrine sweat, may have had a role in man in the past, but is now clearly vestigial. Sweat collected from the surface of the skin is contaminated by sebum (since there is a common opening to the surface of the skin), secretions from eccrine sweat glands, as well as bacteria. Based on animal data, it is thought that aprocrine sweat contains protein, nitrogen, potassium, sodium, calcium, magnesium, chloride, bicarbonate and lactate. Sweat is secreted in a pulsatile manner, presumably due to synchronous contraction of myoepithelial cells across the body.
Unlike eccrine glands which are under cholinergic control, apocrine gland secretion is largely under adrenergic control. Both local and circulating epinephrine and norepinephrine can stimulate secretion. Emotional stimuli, after puberty, are strong inducers of secretion. Drugs that affect the adrenergic system (such as reserpine) affect apocrine gland secretion. 5.alpha.-Reductase levels are very high in apocrine glands. Therefore, activity of this enzyme is believed to play a role in controlling secretion. However, a 5.alpha.-reductase inhibitor has not been previously studied as an inhibitor of apocrine secretion.
Hyperhidrosis is defined as an increase above normal in sweat production. This is diagnosed when sweating occurs under conditions where it would not normally be expected or is excessive in response to emotional or thermal stimuli.
Localized hyperhidrosis of the axilla is most likely due to a combination of increased eccrine and apocrine sweat production. This disorder is usually most problematic when there is both an increased ambient temperature and emotional stimulation. Axillary sweating, unlike eccrine sweating, is largely resistant to most common antiperspirant regimens. Aluminum salts or anticholinergic agents produce only a 50% decrease in armpit sweating, but nearly a 100% decrease in eccrine sweating elsewhere. However, Shelley described a regimen of aluminum chloride in absolute ethanol or isopropyl alcohol under occlusive plastic wrap at bedtime which more effectively inhibits axillary sweat. Other reported treatments are sympathectomy of the fifth thoracic ganglion, local excision of affected axillary skin, cryosurgery, tranquilizers and anticholinergic agents.
Hydradenitis suppurativa (HS) is a chronic inflammatory disorder of apocrine sweat glands in which abscesses and drainage sinuses develop in the axilla and/or perineal area. The pathogenesis of HS is felt to be similar to acne: poral occlusion, bacterial colonization, androgenic stimulation and inflammation all seem to be important. Although its etiology is multifactorial, it is likely that a change in any one of the four etiologic factors will have a significant impact on the course of the disease. Antibiotics (affecting bacterial colonization) and isotretinoin (ACCUTANE.RTM.) (affecting the keratinous plugging of the sweat duct) are used to treat this disorder. Antiandrogens such as cyproterone (not available in the U.S.) and estrogen have also been used to control HS.
The enzyme 5.alpha.-reductase converts testosterone ("T") to dihydrotestosterone in certain target organs as well as in the circulating blood serum. It is known that inhibitors of 5.alpha.-reductase will serve to prevent or lessen symptoms of hyperandrogenic stimulation such as acne vulgaris, seborrhea, female hirsutism, androgenic alopecia, and benign prostatic hyperplasia. See especially U.S. Pat. Nos. 4,377,584 and 4,760,07 1, both assigned to Merck & Co., Inc. It is also now known that two isozymes of 560 -reductase exist: isozyme type 2 which principally interacts within prostatic tissues, and isozyme type 1, discovered more recently, which principally interacts within skin tissues. See, e.g., G. Hams, et al., Proc. Natl. ACad. Sci. USA, vol. 89, pp. 10787-10791 (November 1992).
Since androgens are felt to play a role in the pubertal onset of aprocrine gland function and the pathogenesis of HS and there is a large amount of 5.alpha.-reductase activity in apocrine sweat glands, apocrine sweat gland production should be decreased by 5.alpha.-reductase inhibitors, such as finasteride (marketed in the U.S. under the tradename PROSCAR.RTM. for the treatment of benign prostatic hyperplasia) and 4,7.beta.-dimethyl-4-aza-5.alpha.-cholestan-3-one (also known as MK-386). A decrease in sweat production, should be observed with either oral administration or topical application of 5.alpha.-reductase inhibitors to the axillae or perineum. Therefore, these agents will be useful as antiperspirants and for the treatment of other androgenmediated conditions related to sweat glands, such as local hyperhidrosis and HS.